The Experts below are selected from a list of 273 Experts worldwide ranked by ideXlab platform
Leo C James - One of the best experts on this subject based on the ideXlab platform.
-
aaa atpase p97 vcp is essential for trim21 mediated Virus Neutralization
Proceedings of the National Academy of Sciences of the United States of America, 2012Co-Authors: Felix Hauler, Donna L Mallery, William A Mcewan, Susanna R Bidgood, Leo C JamesAbstract:Tripartite motif-containing 21 (TRIM21) is a cytosolic IgG receptor that mediates intracellular Virus Neutralization by antibody. TRIM21 targets virions for destruction in the proteasome, but it is unclear how a substrate as large as a viral capsid is degraded. Here, we identify the ATPase p97/valosin-containing protein (VCP), an enzyme with segregase and unfoldase activity, as a key player in this process. Depletion or catalytic inhibition of VCP prevents capsid degradation and reduces Neutralization. VCP is required concurrently with the proteasome, as addition of inhibitor after proteasomal degradation has no effect. Moreover, our results suggest that it is the challenging nature of Virus as a substrate that necessitates involvement of VCP, since intracellularly expressed IgG Fc is degraded in a VCP-independent manner. These results implicate VCP as an important host factor in antiviral immunity.
-
AAA ATPase p97/VCP is essential for TRIM21-mediated Virus Neutralization
Proceedings of the National Academy of Sciences of the United States of America, 2012Co-Authors: Felix Hauler, Donna L Mallery, William A Mcewan, Susanna R Bidgood, Leo C JamesAbstract:Tripartite motif-containing 21 (TRIM21) is a cytosolic IgG receptor that mediates intracellular Virus Neutralization by antibody. TRIM21 targets virions for destruction in the proteasome, but it is unclear how a substrate as large as a viral capsid is degraded. Here, we identify the ATPase p97/valosin-containing protein (VCP), an enzyme with segregase and unfoldase activity, as a key player in this process. Depletion or catalytic inhibition of VCP prevents capsid degradation and reduces Neutralization. VCP is required concurrently with the proteasome, as addition of inhibitor after proteasomal degradation has no effect. Moreover, our results suggest that it is the challenging nature of Virus as a substrate that necessitates involvement of VCP, since intracellularly expressed IgG Fc is degraded in a VCP-independent manner. These results implicate VCP as an important host factor in antiviral immunity.
-
regulation of Virus Neutralization and the persistent fraction by trim21
Journal of Virology, 2012Co-Authors: William A Mcewan, C R Williams, R A Crowther, Felix Hauler, Donna L Mallery, Susanna R Bidgood, Leo C JamesAbstract:Despite a central role in immunity, antibody Neutralization of Virus infection is poorly understood. Here we show how the Neutralization and persistence of adenoVirus type 5, a prevalent nonenveloped human Virus, are dependent upon the intracellular antibody receptor TRIM21. Cells with insufficient amounts of TRIM21 are readily infected, even at saturating concentrations of neutralizing antibody. Conversely, high TRIM21 expression levels decrease the persistent fraction of the infecting Virus and allows Neutralization by as few as 1.6 antibody molecules per Virus. The direct interaction between TRIM21 and neutralizing antibody is essential, as single-point mutations within the TRIM21-binding site in the Fc region of a potently neutralizing antibody impair Neutralization. However, infection at high multiplicity can saturate TRIM21 and overcome Neutralization. These results provide insight into the mechanism and importance of a newly discovered, effector-driven process of antibody Neutralization of nonenveloped Viruses.
Peter D Kwong - One of the best experts on this subject based on the ideXlab platform.
-
structural basis of respiratory syncytial Virus Neutralization by motavizumab
Nature Structural & Molecular Biology, 2010Co-Authors: Jason S Mclellan, Man Chen, Albert Kim, Yongping Yang, Barney S Graham, Peter D KwongAbstract:Respiratory syncytial Virus (RSV) is a highly contagious illness in young children. The structure of antibody drug motavizumab in complex with a 24-residue peptide corresponding to its epitope on RSV-fusion glycoprotein suggests why it is more potent than its predecessor, palivizumab (Synagis).
Felix Hauler - One of the best experts on this subject based on the ideXlab platform.
-
aaa atpase p97 vcp is essential for trim21 mediated Virus Neutralization
Proceedings of the National Academy of Sciences of the United States of America, 2012Co-Authors: Felix Hauler, Donna L Mallery, William A Mcewan, Susanna R Bidgood, Leo C JamesAbstract:Tripartite motif-containing 21 (TRIM21) is a cytosolic IgG receptor that mediates intracellular Virus Neutralization by antibody. TRIM21 targets virions for destruction in the proteasome, but it is unclear how a substrate as large as a viral capsid is degraded. Here, we identify the ATPase p97/valosin-containing protein (VCP), an enzyme with segregase and unfoldase activity, as a key player in this process. Depletion or catalytic inhibition of VCP prevents capsid degradation and reduces Neutralization. VCP is required concurrently with the proteasome, as addition of inhibitor after proteasomal degradation has no effect. Moreover, our results suggest that it is the challenging nature of Virus as a substrate that necessitates involvement of VCP, since intracellularly expressed IgG Fc is degraded in a VCP-independent manner. These results implicate VCP as an important host factor in antiviral immunity.
-
AAA ATPase p97/VCP is essential for TRIM21-mediated Virus Neutralization
Proceedings of the National Academy of Sciences of the United States of America, 2012Co-Authors: Felix Hauler, Donna L Mallery, William A Mcewan, Susanna R Bidgood, Leo C JamesAbstract:Tripartite motif-containing 21 (TRIM21) is a cytosolic IgG receptor that mediates intracellular Virus Neutralization by antibody. TRIM21 targets virions for destruction in the proteasome, but it is unclear how a substrate as large as a viral capsid is degraded. Here, we identify the ATPase p97/valosin-containing protein (VCP), an enzyme with segregase and unfoldase activity, as a key player in this process. Depletion or catalytic inhibition of VCP prevents capsid degradation and reduces Neutralization. VCP is required concurrently with the proteasome, as addition of inhibitor after proteasomal degradation has no effect. Moreover, our results suggest that it is the challenging nature of Virus as a substrate that necessitates involvement of VCP, since intracellularly expressed IgG Fc is degraded in a VCP-independent manner. These results implicate VCP as an important host factor in antiviral immunity.
-
regulation of Virus Neutralization and the persistent fraction by trim21
Journal of Virology, 2012Co-Authors: William A Mcewan, C R Williams, R A Crowther, Felix Hauler, Donna L Mallery, Susanna R Bidgood, Leo C JamesAbstract:Despite a central role in immunity, antibody Neutralization of Virus infection is poorly understood. Here we show how the Neutralization and persistence of adenoVirus type 5, a prevalent nonenveloped human Virus, are dependent upon the intracellular antibody receptor TRIM21. Cells with insufficient amounts of TRIM21 are readily infected, even at saturating concentrations of neutralizing antibody. Conversely, high TRIM21 expression levels decrease the persistent fraction of the infecting Virus and allows Neutralization by as few as 1.6 antibody molecules per Virus. The direct interaction between TRIM21 and neutralizing antibody is essential, as single-point mutations within the TRIM21-binding site in the Fc region of a potently neutralizing antibody impair Neutralization. However, infection at high multiplicity can saturate TRIM21 and overcome Neutralization. These results provide insight into the mechanism and importance of a newly discovered, effector-driven process of antibody Neutralization of nonenveloped Viruses.
Jason S Mclellan - One of the best experts on this subject based on the ideXlab platform.
-
structural basis of respiratory syncytial Virus Neutralization by motavizumab
Nature Structural & Molecular Biology, 2010Co-Authors: Jason S Mclellan, Man Chen, Albert Kim, Yongping Yang, Barney S Graham, Peter D KwongAbstract:Respiratory syncytial Virus (RSV) is a highly contagious illness in young children. The structure of antibody drug motavizumab in complex with a 24-residue peptide corresponding to its epitope on RSV-fusion glycoprotein suggests why it is more potent than its predecessor, palivizumab (Synagis).
William A Mcewan - One of the best experts on this subject based on the ideXlab platform.
-
aaa atpase p97 vcp is essential for trim21 mediated Virus Neutralization
Proceedings of the National Academy of Sciences of the United States of America, 2012Co-Authors: Felix Hauler, Donna L Mallery, William A Mcewan, Susanna R Bidgood, Leo C JamesAbstract:Tripartite motif-containing 21 (TRIM21) is a cytosolic IgG receptor that mediates intracellular Virus Neutralization by antibody. TRIM21 targets virions for destruction in the proteasome, but it is unclear how a substrate as large as a viral capsid is degraded. Here, we identify the ATPase p97/valosin-containing protein (VCP), an enzyme with segregase and unfoldase activity, as a key player in this process. Depletion or catalytic inhibition of VCP prevents capsid degradation and reduces Neutralization. VCP is required concurrently with the proteasome, as addition of inhibitor after proteasomal degradation has no effect. Moreover, our results suggest that it is the challenging nature of Virus as a substrate that necessitates involvement of VCP, since intracellularly expressed IgG Fc is degraded in a VCP-independent manner. These results implicate VCP as an important host factor in antiviral immunity.
-
AAA ATPase p97/VCP is essential for TRIM21-mediated Virus Neutralization
Proceedings of the National Academy of Sciences of the United States of America, 2012Co-Authors: Felix Hauler, Donna L Mallery, William A Mcewan, Susanna R Bidgood, Leo C JamesAbstract:Tripartite motif-containing 21 (TRIM21) is a cytosolic IgG receptor that mediates intracellular Virus Neutralization by antibody. TRIM21 targets virions for destruction in the proteasome, but it is unclear how a substrate as large as a viral capsid is degraded. Here, we identify the ATPase p97/valosin-containing protein (VCP), an enzyme with segregase and unfoldase activity, as a key player in this process. Depletion or catalytic inhibition of VCP prevents capsid degradation and reduces Neutralization. VCP is required concurrently with the proteasome, as addition of inhibitor after proteasomal degradation has no effect. Moreover, our results suggest that it is the challenging nature of Virus as a substrate that necessitates involvement of VCP, since intracellularly expressed IgG Fc is degraded in a VCP-independent manner. These results implicate VCP as an important host factor in antiviral immunity.
-
regulation of Virus Neutralization and the persistent fraction by trim21
Journal of Virology, 2012Co-Authors: William A Mcewan, C R Williams, R A Crowther, Felix Hauler, Donna L Mallery, Susanna R Bidgood, Leo C JamesAbstract:Despite a central role in immunity, antibody Neutralization of Virus infection is poorly understood. Here we show how the Neutralization and persistence of adenoVirus type 5, a prevalent nonenveloped human Virus, are dependent upon the intracellular antibody receptor TRIM21. Cells with insufficient amounts of TRIM21 are readily infected, even at saturating concentrations of neutralizing antibody. Conversely, high TRIM21 expression levels decrease the persistent fraction of the infecting Virus and allows Neutralization by as few as 1.6 antibody molecules per Virus. The direct interaction between TRIM21 and neutralizing antibody is essential, as single-point mutations within the TRIM21-binding site in the Fc region of a potently neutralizing antibody impair Neutralization. However, infection at high multiplicity can saturate TRIM21 and overcome Neutralization. These results provide insight into the mechanism and importance of a newly discovered, effector-driven process of antibody Neutralization of nonenveloped Viruses.